Kidney international, 2018-02, Vol.93 (2), p.355-364
2018
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Details
- Autor(en) / Beteiligte
- Titel
- Human plasmacytoid dendritic cells acquire phagocytic capacity by TLR9 ligation in the presence of soluble factors produced by renal epithelial cells
- Ist Teil von
- Kidney international, 2018-02, Vol.93 (2), p.355-364
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2018
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Plasmacytoid dendritic cells (pDCs) are antigen presenting cells specialized in viral recognition through Toll-like receptor (TLR)7 and TLR9, and produce vast amounts of interferon alpha upon ligation of these TLRs. We had previously demonstrated a strong influx of pDCs in the tubulointerstitium of renal biopsies at the time of acute rejection. However, the role of human pDCs in mediating acute or chronic allograft rejection remains elusive. pDCs are thought to have a limited capacity to ingest apoptotic cells, critical for inducing CD4+ T cell activation via indirect antigen presentation and subsequent activation of antibody producing B cells. Here we tested whether the function of pDCs is affected by their presence within the graft. Maturation and interferon alpha production by pDCs was enhanced when cells were activated in the presence of viable HK2 renal epithelial cells. Importantly, soluble factors produced by cytomegalovirus-infected (primary) epithelial or endothelial cells enhanced pDC activation and induced their capacity to phagocytose apoptotic cells. Phagocytosis was not induced by free virus or soluble factors from non-infected cells. Activated pDCs showed an enhanced CD4+ and CD8+ T cell allostimulatory capacity as well as a potent indirect alloantigen presentation. Granulocyte Macrophage-Colony Stimulating Factor is one of the soluble factors produced by renal epithelial cells that, combined with TLR9 ligation, induced this functional capacity. Thus, pDCs present in the rejecting allograft can contribute to alloimmunity and potentially act as important orchestrators in the manifestation of acute and chronic rejection.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0085-2538eISSN: 1523-1755DOI: 10.1016/j.kint.2017.08.006Titel-ID: cdi_proquest_miscellaneous_1955066779
- Format
- –
- Schlagworte
- acute rejection, Antigen Presentation, Antigen-presenting cells, Antigens, Apoptosis, Biopsy, CD4 antigen, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - metabolism, CD8 antigen, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - metabolism, Cell activation, Cell Line, chronic allograft nephropathy, Cloning, Coculture Techniques, Colony-stimulating factor, Cytokines, Cytomegalovirus, Cytomegalovirus - immunology, Cytomegalovirus - pathogenicity, Dendritic cells, Dendritic Cells - immunology, Dendritic Cells - metabolism, Endothelial cells, endothelium, Enzymes, Epithelial cells, Epithelial Cells - immunology, Epithelial Cells - metabolism, Epithelial Cells - pathology, Epithelial Cells - virology, Flow cytometry, Graft rejection, Graft Rejection - immunology, Graft Rejection - metabolism, Graft Rejection - pathology, Graft Rejection - virology, Granulocyte-macrophage colony-stimulating factor, Granulocyte-Macrophage Colony-Stimulating Factor - immunology, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism, Granulocytes, Host-Pathogen Interactions, Humans, Infections, Interferon-alpha - metabolism, Isoantigens - immunology, Isoantigens - metabolism, Kidney Transplantation - adverse effects, Kidney Tubules, Proximal - immunology, Kidney Tubules, Proximal - metabolism, Kidney Tubules, Proximal - pathology, Kidney Tubules, Proximal - virology, Kidneys, Leukocytes (granulocytic), Lymphocyte Activation, lymphocytes, Lymphocytes B, Lymphocytes T, Macrophages, Paracrine Communication, Phagocytes, Phagocytosis, Phenotype, Signal Transduction, Statistical analysis, T cell receptors, TLR9 protein, Toll-Like Receptor 9 - immunology, Toll-Like Receptor 9 - metabolism, Toll-like receptors, Viral infections, α-Interferon